Today, type-II diabetics are continuously increasing in Japan, and the estimated number of the same exceeds 8,200,000. As a measure against this increase, interventions for preventing diabetes from developing have been made based on the glucose tolerance test, resulting, however, in unsatisfactory effects. The cause is as follows: at such a borderline stage that functional abnormalities are found by the glucose tolerance test, disorders of pancreatic islets have already advanced to a high degree, and this stage possibly is too late as a time for starting interventions.
More specifically, in the diabetes developing process, the amount of pancreatic islets (particularly, the amount of pancreatic β-cells) decreases prior to the occurrence of glucose tolerance abnormalities. Therefore, when functional abnormalities are detected or there are subjective symptoms, diabetes has already reached the stage where it is too difficult to be treated. On the other hand, if a decrease in the amount of pancreatic islets and/or the amount of pancreatic β-cells can be detected at an early stage, there is a possibility for the prevention and treatment of diabetes. Therefore, a technique for noninvasive imaging of pancreatic islets, particularly a technique for noninvasive imaging of pancreatic islets for determining the amount of pancreatic islets and/or the amount of pancreatic β-cells, has been desired for prevention and diagnosis of diabetes. Among these, a molecular probe that enables noninvasive imaging of pancreatic islets, preferably pancreatic β-cells, and noninvasive determination of an amount of pancreatic β-cells has been desired in particular.
In designing a molecular probe for imaging of pancreatic islets, various target molecules in pancreatic cells, particularly functional proteins specific in the β-cells, are being researched. Among these, GLP-1R (glucagon-like peptide-1 receptor) is being researched as a target molecule; GLP-1R is distributed in pancreatic β-cells, and is seven-transmembrane G protein coupled receptor.
As molecular probes for imaging that use GLP-1R as a target molecule, the following are researched: a peptide derivative of GLP-1; a peptide derivative of exendin-3; and a peptide derivative of exendin-4 (e.g., Patent Document 1).
Further, the following, for example, also are researched: a molecular probe obtained by labeling a derivative of exendin-4(9-39) as a GLP-1R antagonist with [18F] fluorine (e.g., Non-Patent Document 1); a molecular probe obtained by labeling a derivative of exendin-4 as an GLP-1R agonist with [111In] indium via diethylenetriaminepentaacetic acid (DTPA) (e.g., Non-Patent Documents 2 and 3); and a molecular probe obtained by labeling a derivative of exendin-4(9-39) as a GLP-1R antagonist with [111In] indium via DTPA (e.g., Non-Patent Document 3).
However, a novel molecular probe for imaging is desired that enables noninvasive three-dimensional imaging of pancreatic islets.